Helminth-microbe interactions in the vertebrate gut: Effects on host health and susceptibility to disease

Abstract

The vertebrate gastrointestinal tract harbors a diverse and complex community of microbes, known as the microbiota. This ecological community lives in an intimate symbiosis with its host, influencing host development, immunity, metabolism, and disease. These microbes also share their habitat with a diverse group of eukaryotes, including protozoa, fungi, and helminths, many of which are well-known parasites. Helminths in particular have co-evolved with vertebrate hosts for hundreds of millions of years and have helped shape the vertebrate immune system and gut microbiota. Thus, vertebrates often require the presence of both the commensal microbiota as well as the gut macrobiota for intestinal immune homeostasis. However, little is still known about the interactions between microbes and helminths in the vertebrate gut and the consequences of these interactions on host health and disease. As increased hygiene, industrialization, and medical interventions continue to lower the diversity and abundances of these intestinal inhabitants in hosts, a clearer understanding of how these communities interact to influence host physiology is needed.

In this dissertation, I investigate potential mechanisms driving helminth-microbe interactions in the vertebrate gut and the effects these interactions have on host susceptibility to disease. Synthesizing the current literature on helminth-microbiota interactions in vertebrates, I describe how alterations to the physical and immune landscapes of the gut may directly and/or indirectly impact the gut microbial community and infection outcomes. I then investigate helminth-microbe interactions in both mice and humans to uncover how microbes may impact susceptibility to helminth infection, and how helminth colonization and removal in turn influences the commensal and pathogenic communities of the gut. Understanding the mechanisms by which helminths and gut microbes interact in the vertebrate gut can ultimately help predict the impacts these communities have host health and disease and can lead to improved treatments for helminth infections and dysbiosis of the gut microbiota.